Abstract: Our phenotype includes not only physical features, but also behavioral outputs such as motor schemes and learned skills, and is the result of a complex interaction between genetic background and environment. In fact, a good fraction of last decades’ biomedical efforts were dedicated to understanding how different elements (e.g., genetic polymorphisms, lifestyle components) participate in this interplay, ultimately contributing to affect a given phenotype up to the point of steering it towards pathology. Genetic and epigenetic elements are relatively easy to analyze individually using a reductionist approach, for instance via loss- or gain-of-function studies in cellular and animal models; the effects of nutrients, drugs, pollutants can be similarly tested as single specific stimuli. Not as easy is to establish in rigorous terms and to understand the molecular mechanisms through which different levels of education, social interaction, exposure to a playful environment, psychological stress, to voluntary physical activity, may impact our brain phenotype, whose combined complexity is hard to reproduce in the experimental setting.